NCT01618071

Brief Summary

Many types of cardiovascular disease begin when the layer of cells lining blood vessels (endothelial cells) start to function abnormally. This causes white blood cells (monocytes) to enter the blood vessel wall and eventually form lesions. Fats from foods we consume are carried in the blood for 3-8 hours after a fatty meal in small particles known as chylomicrons (CM) and chylomicron remnants (CMR). The overall aim of this project is to investigate the idea that n-3 polyunsaturated fatty acids (PUFA) protect against heart disease by modifying the effect of CMR on endothelial cells and monocytes. We hypothesize that n3-PUFA carried in CMR reduce detrimental events which promote blood vessel damage and activate protective mechanisms to improve the function of arteries.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jun 2012

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2012

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

June 8, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 13, 2012

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2012

Completed
Last Updated

September 16, 2019

Status Verified

September 1, 2019

Enrollment Period

4 months

First QC Date

June 8, 2012

Last Update Submit

September 12, 2019

Conditions

Postprandial PeriodLipemiaVasodilationVascular ResistanceNitric Oxide

Keywords

n-3 PUFAEndothelial cellsNitric oxideOxidative stressBlood pressureVasodilationLipemiaUnsaturated dietary fats

Outcome Measures

Primary Outcomes (1)

  • Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction

    The primary outcome of the study is activation of inflammatory/oxidative stress pathways within cultured endothelial cells following incubation with pooled postprandial lipoprotein fractions rich in chylomicron remnants. Due to the nature of this type of research this necessitates more than one primary outcome measure: the primary measures are NF-kappa-beta activation, cytokine production (e.g. interleukin-6) and reactive oxygen species generation in the cultured human endothelial cells.

    6 h post-meal

Secondary Outcomes (14)

  • Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol

    0, 1, 2, 3, 4, 5 and 6 h post-meal

  • Incremental area under the plasma concentration versus time curve (iAUC) of glucose

    0, 1, 2, 3, 4, 5 and 6 h post-meal

  • Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids

    0, 1, 2, 3, 4, 5 and 6 h post-meal

  • Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%)

    0, 1, 2, 3, 4, 5 and 6 h post-meal

  • Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol

    0, 1, 2, 3, 4, 5 and 6 h post-meal

  • +9 more secondary outcomes

Study Arms (4)

Oleic acid

ACTIVE COMPARATOR

75 g high oleic acid sunflower oil.

Dietary Supplement: High-fat meals varying in their fatty acid composition

Linoleic acid

ACTIVE COMPARATOR

75 g high linoleic acid sunflower oil.

Dietary Supplement: High-fat meals varying in their fatty acid composition

Eicosapentaenoic acid and docosahexaenoic acid

EXPERIMENTAL

5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.

Dietary Supplement: High-fat meals varying in their fatty acid composition

Docosahexaenoic acid

EXPERIMENTAL

5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.

Dietary Supplement: High-fat meals varying in their fatty acid composition

Interventions

High-fat meals varying in their fatty acid compositionDIETARY_SUPPLEMENT

70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements

Also known as: DHASCO, Purified fish oil
Docosahexaenoic acidEicosapentaenoic acid and docosahexaenoic acidLinoleic acidOleic acid

Eligibility Criteria

Age35 Years - 70 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy males
  • Non-smokers
  • Aged 35-70 years
  • Fasting TAG concentrations ≥1.2 mmol/L.

You may not qualify if:

  • Reported history of CVD (myocardial infarction, angina, venous thrombosis, stroke), impaired fasting glucose/uncontrolled type 2 diabetes (or fasting glucose ≥ 6.1 mmol/L), cancer, kidney, liver or bowel disease.
  • Presence of gastrointestinal disorder or use of drug, which is likely to alter gastrointestinal motility or nutrient absorption.
  • History of substance abuse or alcoholism (previous weekly alcohol intake \>60 units/men)
  • Current self-reported weekly alcohol intake exceeding 28 units
  • Allergy or intolerance to any component of test meals
  • Unwilling to restrict consumption of any source of fish oil for the length of the study
  • Weight change of \>3kg in preceding 2 months
  • Body Mass Index \<20 and \>35 kg/m2
  • Fasting blood cholesterol \> 7.8 mmol/L
  • Current cigarette smoker.
  • Current use of lipid lowering medication

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Diabetes & Nutritional Sciences Division, King's College London

London, SE1 9NH, United Kingdom

Location

Related Publications (10)

  • Lambert MS, Botham KM, Mayes PA. Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants. Br J Nutr. 1996 Sep;76(3):435-45. doi: 10.1079/bjn19960048.

    PMID: 8881715BACKGROUND

  • Botham KM, Bravo E, Elliott J, Wheeler-Jones CP. Direct interaction of dietary lipids carried in chylomicron remnants with cells of the artery wall: implications for atherosclerosis development. Curr Pharm Des. 2005;11(28):3681-95. doi: 10.2174/138161205774580732.

    PMID: 16305504BACKGROUND

  • Proctor SD, Vine DF, Mamo JC. Arterial retention of apolipoprotein B(48)- and B(100)-containing lipoproteins in atherogenesis. Curr Opin Lipidol. 2002 Oct;13(5):461-70. doi: 10.1097/00041433-200210000-00001.

    PMID: 12352009BACKGROUND

  • Marcoux C, Hopkins PN, Wang T, Leary ET, Nakajima K, Davignon J, Cohn JS. Remnant-like particle cholesterol and triglyceride levels of hypertriglyceridemic patients in the fed and fasted state. J Lipid Res. 2000 Sep;41(9):1428-36.

    PMID: 10974050BACKGROUND

  • Hall WL, Sanders KA, Sanders TA, Chowienczyk PJ. A high-fat meal enriched with eicosapentaenoic acid reduces postprandial arterial stiffness measured by digital volume pulse analysis in healthy men. J Nutr. 2008 Feb;138(2):287-91. doi: 10.1093/jn/138.2.287.

    PMID: 18203893BACKGROUND

  • Burdge GC, Powell J, Dadd T, Talbot D, Civil J, Calder PC. Acute consumption of fish oil improves postprandial VLDL profiles in healthy men aged 50-65 years. Br J Nutr. 2009 Jul;102(1):160-5. doi: 10.1017/S0007114508143550. Epub 2009 Jan 13.

    PMID: 19138437BACKGROUND

  • Zampelas A, Peel AS, Gould BJ, Wright J, Williams CM. Polyunsaturated fatty acids of the n-6 and n-3 series: effects on postprandial lipid and apolipoprotein levels in healthy men. Eur J Clin Nutr. 1994 Dec;48(12):842-8.

    PMID: 7889892BACKGROUND

  • Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Clin Sci (Lond). 2008 Jun;114(11):679-86. doi: 10.1042/CS20070277.

    PMID: 18052925BACKGROUND

  • Rontoyanni VG, Hall WL, Pombo-Rodrigues S, Appleton A, Chung R, Sanders TA. A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA. Br J Nutr. 2012 Aug;108(3):492-9. doi: 10.1017/S0007114511005721. Epub 2012 Feb 21.

    PMID: 22348439BACKGROUND

  • Purcell R, Latham SH, Botham KM, Hall WL, Wheeler-Jones CP. High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2alpha concentrations relative to a control high-oleic acid meal: a randomized controlled trial. Am J Clin Nutr. 2014 Oct;100(4):1019-28. doi: 10.3945/ajcn.114.091223. Epub 2014 Aug 6.

    PMID: 25099540DERIVED

Related Links

MeSH Terms

Conditions

HyperlipidemiasAneurysm

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Wendy L Hall, PhD

    King's College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Lecturer in Nutritional Sciences

Study Record Dates

First Submitted

June 8, 2012

First Posted

June 13, 2012

Study Start

June 1, 2012

Primary Completion

October 1, 2012

Study Completion

October 1, 2012

Last Updated

September 16, 2019

Record last verified: 2019-09

Locations

GB(1)